Molecular Genetics and Genomics最新文献

Salt mine workers are occupationally exposed to DNA damaging agents at their workplace. The present study estimates the extent of DNA damage and expression deregulation of related genes in mine workers, staff, community living nearby and unexposed controls. Blood samples were collected from all groups. Expression analysis of AGT, H2AX and Mre11 genes was done using RT-PCR. DNA damage was detected by comet assay. Relative expression of selected genes was upregulated in mine, staff and community group compared to control. Expression of all three genes increased significantly with increasing age, total exposure time and smoking. DNA damage was higher in mine workers compared to control, staff and community groups. Elevated serum levels of sodium, potassium, chloride and total ROS were observed in mine and staff group compared to control and community group. Positive correlation was observed between gene expression versus total exposure time. Moreover, significant dependable regression was observed between gene expression versus comet parameters. The present study anticipated a negative impact of mine environment on the genomic stability of mine workers and staff group. Moreover, age, exposure time and smoking act synergistically to enhance the extent of DNA damage, ROS production, electrolyte imbalance and expression deregulation of selected genes. In addition, current research will provoke thoughtful insights to rethink the risk assessments for genetic integrity of community living nearby mines.

Fennel (Foeniculum vulgare Mill.) is a widely cultivated medicinal and aromatic plant valued for its essential oils used in pharmaceutical, culinary, and industrial applications. Breeding activities for fennel have been historically limited, but recent genomic advances have revealed substantial genetic diversity and variability among its populations, offering new opportunities to improve yield, oil composition, and stress resilience. Studies using molecular markers including RAPD, ISSR, SSR, and SNPs have characterized the genetic structure of fennel germplasm and identified key loci for traits such as seed yield, essential oil profile, and disease tolerance. Quantitative trait locus (QTL) mapping and principal component analysis (PCA) have refined genotype selection. Transcriptomic studies related to t-anethole biosynthesis and expression profiles under stress conditions have enabled functional gene discovery. Biotechnological tools such as callus induction, doubled haploid protocols, and in vitro selection techniques have emerged as adjunct strategies to accelerate breeding outcomes. Integration of classical breeding methods with molecular and biotechnological approaches enables precision breeding of fennel cultivars tailored for modern agricultural needs. Enhancing genetic diversity utilization and targeting key traits will support the development of high-performing, resilient varieties. This direction advances both the sustainability of fennel cultivation and its utility in agro-industrial sectors.

An introgression from Moricandia arvensis is known to restore male fertility to Brassica juncea cytoplasmic male sterile lines carrying M. arvensis, Diplotaxis berthautii, D. catholica or D. erucoides cytoplasm. We have previously mapped the fertility-restorer gene (Rfm) to the distal end of A09 chromosome of B. juncea but the restorer gene remains to be discovered. This study was undertaken to identify and clone the restorer gene(s) using next-generation sequencing approach, leveraging its known chromosomal location and flanking markers. We assembled the draft genome of the B. juncea fertility restorer line (MRS15), carrying the M. arvensis introgression. Alignment of the MRS15 genomic scaffolds to B. juncea reference genome identified six scaffolds aligned to the terminal region of chromosome A09 (between 51 and 58.5 Mb) harbouring the Rfm. The high-density linkage map of Rfm locus confirmed the correct orientation of these scaffolds. Based on segregation of tightly linked flanking markers, namely, the earlier reported BjESSR06 and a newly identified SRB17 marker, the Rfm gene was assigned to Scaffold-547. In silico analysis revealed six pentatricopeptide repeat (PPR)-encoding Restorer-of-Fertility-Like (RFL) genes in the ~ 300 kb region delimited by the above stated markers. Based on the expression profiles of these genes in CMS and fertility restorer lines, and in a segregating population, PPR-640 was identified as the Rfm gene. Further, we designed a gene-based, co-dominant marker perfectly co-segregating with fertility restorer trait through collinearity analysis of the genomic region spanning PPR-640 and the B. juncea genome. The Rfm gene and the marker reported here are critical for utilising this CMS system in hybrid breeding and to clone and study evolution of restorer genes in other Brassicaceae members.

Oncogenic Ras mutations are prevalent in human cancers, yet the mechanisms by which Ras promotes tumorigenesis remain incompletely understood. In Drosophila, oncogenic Ras (Ras^V12) induces tissue overgrowth and metastasis, but the cellular restraints it must overcome are unclear. We have identified Drosophila CRIF, the homolog of mammalian CR6-interacting factor 1 (CRIF1), as a modifier of Ras^V12-induced lethality and Ras^V12-induced overgrowth and cell proliferation. Knockdown of CRIF exacerbated Ras^V12 phenotypes, while CRIF overexpression ameliorated them. Further, we found that CRIF was also required for heterochromatin formation, as loss of CRIF suppressed position-effect variegation (PEV) and reduced the levels of Heterochromatin Proteins 1 (HP1) and Histone H3 Lysine 9 trimethylation (H3K9me3). CRIF physically interacted with HP1, suggesting a role in recruiting HP1 to heterochromatin. Notably, CRIF did not regulate HP1 transcription or total protein levels but influenced HP1 localization. Our findings demonstrate that CRIF functions as a tumor suppressor by negatively regulating cell proliferation and maintaining heterochromatin stability. CRIF's interaction with HP1 and its role in heterochromatin regulation suggest a novel mechanism linking heterochromatin to tumor suppression in Ras-driven cancers. These results highlight CRIF as a potential therapeutic target and provide new insights into the interplay between chromatin regulation and oncogenic signaling.

Mutations in the STRC gene are a major cause of autosomal recessive mild-to-moderate sensorineural hearing loss (SNHL); however, its prevalence and mutational spectrum in the Chinese population remain largely unexplored. To address this, we analyzed 1015 unrelated Chinese patients with bilateral SNHL using whole-exome sequencing (WES), multiplex ligation-dependent probe amplification (MLPA), and Sanger sequencing. Biallelic STRC variants were identified in 2.1% of all patients, with the diagnostic yield significantly rising to 15.6% among mild-to-moderate SNHL cases. Copy number variants (CNVs) were predominant (90.5%, 19/21), which were potentially mediated by non-allelic homologous recombination (NAHR) involving the pseudogene STRCP1. Notably, 26.2% (11/42) of mutant alleles harbored CNVs spanning both STRC and the adjacent CATSPER2 gene, highlighting critical implications for clinical management and genetic counseling due to potential syndromic associations. MLPA detected additional CNVs missed by WES, emphasizing the necessity of combining multiple genetic testing strategies. Audiologically, patients with biallelic STRC variants exhibited a distinctive frequency-dependent hearing loss, characterized by mild impairment at low frequencies (0.125-0.5 kHz) and moderate to moderately severe impairment at higher frequencies (0.5-8 kHz). These findings highlight the critical importance of CNV detection for genetic diagnosis and clinical management of STRC-related SNHL, particularly in mild-to-moderate cases, and provide essential insights for genetic counseling involving co-occurring STRC and CATSPER2 CNVs.

Although karyotyping technology has been implemented in genetic diagnosis for a long time, the comprehensive understanding of this technology is still limited. The aim of this study was to investigate the accuracy and resolution of karyotyping method in detecting chromosomal abnormalities by molecular genetic method. In this study, we conducted a retrospective analysis of embryonic molecular karyotypes and peripheral blood cytogenetic karyotypes from patients with balanced chromosomal rearrangements undergoing preimplantation genetic testing at our reproductive center. Blood karyotyping was performed using routine G-banding at the 400-band resolution by two well-trained technicians. The embryonic molecular karyotypes were detected using either high-throughput sequencing or single nucleotide polymorphism microarray method. We compared the breakpoint locations, determined by unbalanced rearrangements, in the embryonic molecular karyotypes with the corresponding rearranged chromosome bands in the peripheral blood karyotypes. A total of 508 cases were enrolled and 2078 embryos were detected, 404 cases were analyzed finally. We found that only 39.32% (289/735) of embryonic molecular breakpoints were located within the rearranged bands identified by peripheral blood karyotyping, while the remaining 60.68% (446/735) fell outside these regions. Our results showed only 73 cases exhibited accurate karyotyping results, indicating an accuracy rate of 18.07%. Furthermore, the average resolution of karyotyping technique was found to be approximately 9.01 megabases (Mb) pairs. These findings provide profound insight into the accuracy and resolution of karyotyping techniques, which can contribute to more precise genetic counseling.

Inguinal hernia (IH) is a common condition with a substantial health burden and emerging evidence suggests that lipid metabolism-related indicators may contribute to its risk. However, the exact role of specific lipid types in causing IH is still unclear. This study aims to investigate whether any of 179 distinct lipid species have a causal impact on IH risk using causal inference. We applied a two-sample Mendelian randomization (MR) framework, integrating lipidomic genome-wide association studies (GWAS) data from 7,174 Finnish individuals with IH summary statistics from the UK Biobank (16,749 cases and 439,599 controls). Linkage disequilibrium pruning and genome-wide significance (P < 5E-8) were used to choose genetic instruments. Primary causal estimates were derived with inverse-variance weighted (IVW) method, and further supported by weighted median (WM) and robust adjusted profile score (RAPS). We employed sensitivity tests, like Cochran's Q for heterogeneity, MR-Egger for directional pleiotropy, Radial MR for outlier detection, and leave-one-out analysis to measure the impact of individual variants. Among 179 lipid species, 162 had valid IVs, and 94 met the criteria for causal inference. IVW analysis identified 25 lipid species with nominal significance, 24 of which were supported by WM and RAPS. Sensitivity analyses consistently provided robust evidence supporting a causal relationship between four lipid species and increased IH risk: diacylglycerol (18:1_18:1) (OR = 1.16, P = 0.005), diacylglycerol (18:1_18:2) (OR = 1.12, P = 0.006), phosphatidylinositol (18:0_20:4) (OR = 1.10, P = 1.47E-04), and triacylglycerol (54:6) (OR = 1.21, P = 0.001). Our findings provides genetic molecular evidence that four lipid species are causally linked to an increased IH susceptibility, offering novel insights into lipid-centered interventions for disease prevention and highlighting the importance of metabolic health in hernia pathogenesis.

The gotra system of exogamy is followed by the Brahmin caste group in India. This system restricts the marriage of individuals who belong to the same gotra. In genetic terms, each gotra forms an exogamous group within a population and thereby maintains a lineage. In Koṅkaṇī Sārasvata Brahmins, the gotras are patrilineal. To understand the genetic footprints of the gotras in this population, we reconstructed the maternal and paternal ancestry of 95 individuals using single nucleotide polymorphism (SNP) markers and Y-chromosomal short tandem repeats (Y-STR). The haplogroup distribution in the gotras showed a significant association with the paternal lineage (p < 0.005) as compared with the maternal lineage. We observed a similar significant association of the gotras with the Y-STR haplotypes. Our findings provide scientific evidence for an actively existing gotra system followed by the caste groups of India. Comparative analysis of 334 Indian Brahmins and over 1300 Eurasian Y-STR profiles showed that all Brahmin groups share a common R1a ancestor with Western Iranian males likely predating the Indo-Iranian split in northern Afghanistan. Whilst North Indian Brahmins shared the lineage with Afghanistan groups, the Koṅkaṇī and southern Brahmins may represent an earlier divergence. The persistence of common gotras throughout India implies the gotra system originated before Brahmin dispersal from north to south. These findings provide genetic evidence for the role of gotra system in shaping Brahmin population structure.